Integrated bioinformatic analysis reveals NOS2 as a novel ferroptosis-related biomarker for pre-eclampsia.

BACKGROUND: Pre-eclampsia (PE) is a common condition in pregnancy; however, methods for early diagnosis and effective treatment options are lacking. Ferroptosis is a newly identified iron-dependent cell death pathway. The aim of this study was to investigate the role of ferroptosis-related genes in PE, the underlying mechanism, and their potential diagnostic value using a bioinformatics approach. METHODS: We downloaded the GSE48424 and GSE98224 datasets from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between PE and healthy pregnancy samples were identified in the GSE48424 dataset and subjected to weighted gene co-expression network analysis; the most relevant modules were intersected with known ferroptosis-related genes to distinctly identify the role of ferroptosis in PE. We further searched transcription factors and microRNAs that are predicted to regulate these ferroptosis-related genes, and patients in the GSE48424 dataset were divided into two groups according to high or low expression of the key ferroptosis-related genes associated with PE. To obtain robust key ferroptosis-related genes in PE, we validated their expression levels in the external dataset GSE98224. Finally, the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay was utilized to access the expression of these genes in the PE and normal blood samples. RESULTS: Six ferroptosis-related genes involved in PE were obtained by overlapping 3661 genes most associated with PE, 565 DEGs between PE and normal samples, and 259 known ferroptosis-related genes. Among these genes, patients with PE displaying lower expression levels of NOS2 and higher expression levels of PTGS2 had a higher ferroptosis potential index. The expression pattern of NOS2 was consistent in the GSE48424 and GSE98224 datasets. RT-qPCR data confirmed that NOS2 expression was more significantly elevated in patients with PE than in those with a normal pregnancy. CONCLUSIONS: Our study explored the diagnostic value of ferroptosis-related genes in PE, and identified NOS2 as the key gene linking ferroptosis and PE, suggesting a new candidate biomarker for early PE diagnosis.

Prediction and prognosis of adverse maternal and foetal/neonatal outcomes in pulmonary hypertension: an observational study and nomogram construction.

BACKGROUND: Pregnant women with pulmonary hypertension (PH) have higher mortality rates and poor foetal/neonatal outcomes. Tools to assess these risk factors are not well established. METHODS: Predictive and prognostic nomograms were constructed using data from a "Development" cohort of 420 pregnant patients with PH, recorded between January 2009 and December 2018. Logistic regression analysis established models to predict the probability of adverse maternal and foetal/neonatal events and overall survival by Cox analysis. An independent "Validation" cohort comprised data of 273 consecutive patients assessed from January 2019 until May 2022. Nomogram performance was evaluated internally and implemented with online software to increase the ease of use. RESULTS: Type I respiratory failure, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide [Formula: see text] 1400 ng/L, arrhythmia, and eclampsia with pre-existing hypertension were independent risk factors for maternal mortality or heart failure. Type I respiratory failure, arrhythmia, general anaesthesia for caesarean section, New York Heart Association functional class, and N-terminal pro-brain natriuretic peptide [Formula: see text] 1400 ng/L were independent predictors of pulmonary hypertension survival during pregnancy. For foetal/neonatal adverse clinical events, type I respiratory failure, arrhythmia, general anaesthesia for caesarean section, parity, platelet count, fibrinogen, and left ventricular systolic diameter were important predictors. Nomogram application for the Development and Validation cohorts showed good discrimination and calibration; decision curve analysis demonstrated their clinical utility. CONCLUSIONS: The nomogram and its online software can be used to analyse individual mortality, heart failure risk, overall survival prediction, and adverse foetal/neonatal clinical events, which may be useful to facilitate early intervention and better survival rates.

Global and national trends in years of life lost and years lived with disability caused by three common gastrointestinal cancers from 1990 to 2019.

BACKGROUND: Gastrointestinal cancers are a critical global cancer burden, and tracking their trends would inform the health policies. METHODS: Trends of years of life lost (YLLs) and years lived with disability (YLDs) caused by three common gastrointestinal cancers were estimated using annual percentage change (EAPC) and age-standardized rate (ASR). Data was extracted from the Global Burden of Disease study 2019. RESULTS: The ASR per 100,000 population-year of YLLs caused by esophageal cancer, stomach cancer, and colorectal cancer were 137.98, 264.15, and 282.51 in 2019, respectively. Their overall trends of YLLs declined during 1990-2019, with the respective EAPCs being - 1.42 (95% Confidence Interval [CI]: - 1.71 to - 1.13), - 2.13 (95%CI: - 2.29 to - 1.96), and - 0.25 (95%CI: - 0.30 to - 0.19). Meanwhile, decreasing trends of YLDs caused by esophageal cancer and stomach cancer were observed, in which the EAPCs were - 0.67 (95%: - 0.94 to - 0.40) and - 0.85 (95%CI: - 0.97 to - 0.73), respectively. However, an increasing trend was seen in that of colorectal cancer (EAPC = 0.83, 95%CI: 0.77 to 0.89). Among countries, the largest decrease in trend of YLLs was that of stomacher cancer in the Republic of Korea (EAPC = - 5.88, 95%CI: - 6.07 to - 5.69). However, pronounced increasing trend of YLDs caused by colorectal cancer occurred in China (EAPC = 4.40, 95%CI: 4.07 to 4.72). CONCLUSIONS: Decreasing trends in YLLs and YLDs caused by esophageal cancer, stomach cancer, and colorectal cancer were observed in most countries and regions, indicating that the great progress had been achieved over the past decades. However, the cancer burden was geographical heterogeneity, and cost-effective measures were still required to decline the burden caused by gastrointestinal cancers.

An exploration of clinical features and factors associated with pain frequency and pain intensity in children with growing pains: a cross-sectional study from Chongqing, China.

Instruction: Growing pains are the most common cause of musculoskeletal pain in children, affecting both children's and caregivers' well-being. The lack of definitive diagnostic criteria complicates diagnosis and treatment. Objectives: This study aims to outline the clinical features and identify factors associated with the frequency and intensity of growing pains in children in Chongqing, China. Methods: A cross-sectional study was conducted in a children's hospital using its Internet hospital follow-up platform. Children initially diagnosed with growing pains between July and September 2022 were enrolled. Sociodemographics, pain locations, duration, frequency, intensity, and potentially related factors were collected. Results: Eight hundred sixty-three children were enrolled (average age: 8.19 ± 3.24 years; 455 boys [52.72%]). Pain frequency was reported as quarterly (62.11%), monthly (24.80%), biweekly (1.74%), weekly (10.08%), and daily (1.27%). The prevalence of mild, moderate, and severe pain was 26.65%, 55.74%, and 17.61%, respectively. The knee was the most common pain location (63.85%), mostly encountered between 4 pm and 5 pm (20.51%). Multivariate analysis revealed that pain frequency negatively correlated with vitamin supplementation during pregnancy, positively correlated with underweight, bad temper, increased exercise, and cold lower extremities. Pain intensity positively correlated with irritability, increased exercise, and pain sensitivity but negatively correlated with age and vitamin supplementation during lactation. Conclusion: Growing pains typically occur on a quarterly basis, predominantly affecting the knees during 4 pm to 5 pm. Factors in sociodemographics, maternal aspect, temperament, and exercise levels can influence pain frequency and intensity. Clinicians should consider these aspects when developing comprehensive strategies for pain management.

Combining experiments and bioinformatics to identify transforming growth factor-ß1 as a key regulator in angiotensin II-induced trophoblast senescence.

INTRODUCTION: Accelerated senescence of trophoblast may cause several diverse pregnancy outcomes; however, the cause of accelerated trophoblast senescence remains unclear. The renin-angiotensin system (RAS) is closely related to organ senescence. Therefore, in the present study, we hypothesized that angiotensin (Ang)II, one of the most important RAS family members, accelerates trophoblast senescence through the transforming growth factor ß-1 (TGF-ß1) pathway. METHODS: AngII and Ang1-7 were used to stimulate pregnant rats. AngII and its inhibitor olmesartan were used to stimulate trophoblast. Thereafter, senescence levels were measured. Furthermore, we used AngII to stimulate trophoblast and utilized RNA-sequencing (RNAseq) to analyze the expression of differentially expressed genes (DEGs). After identifying the overlapping genes by comparing the DEGs and senescence-related genes, we employed CytoHubba software to calculate the top five hub genes and selected TGF-ß1 as the target gene. We transfected the AngII-stimulated trophoblast with TGF-ß1 small interfering RNA (siRNA) and measured the senescence levels. RESULTS: Senescence markers were upregulated in the AngII group compared with that in the control group. Furthermore, following AngII stimulation and RNAseq measurement, we identified 607 DEGs and 13 overlapping genes. The top five hub genes were as follows: PLAU, PTGS2, PDGF-ß, TGF-ß1, and FOXO3. Upon knockdown of TGF-ß1 expression in AngII-stimulated trophoblast using TGF-ß1 siRNA, we observed a downregulation of p53 and p62 mRNA expression. DISCUSSION: AngII accelerates trophoblast senescence through the TGF-ß1 pathway.

Causal association between air pollution and frailty: a Mendelian randomization study.

Backgrounds: Frailty is a significant problem for older persons since it is linked to a number of unfavorable consequences. According to observational researches, air pollution may raise the risk of frailty. We investigated the causal association between frailty and air pollution (including PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides) using Mendelian randomization approach. Methods: We conducted MR analysis using extensive publically accessible GWAS (genome-wide association studies) summary data. The inverse variance weighted (IVW) method was employed as the primary analysis method. The weighted median model, MR-Egger, simple model, and weighted model approaches were chosen for quality control. The Cochran's Q test was utilized to evaluate heterogeneity. Pleiotropy is found using the MR-Egger regression test. The MR-PRESSO method was used to recognize outliers. The leave-one-out strategy was used to conduct the sensitivity analysis. Results: MR results suggested that PM2.5 was statistically significantly associated with frailty [odds ratio (OR) = 1.33; 95%confidence interval (CI) = 1.12-1.58, p = 0.001] in IVW method. We observed no statistical association between PM2.5-10(OR = 1.00, 95% CI = 0.79-1.28, p = 0.979), PM10(OR = 0.91, 95% CI = 0.75-1.11, p = 0.364), nitrogen dioxide (OR = 0.98, 95% CI = 0.85-1.12, p = 0.730), nitrogen oxides (OR = 1.15, 95% CI = 0.98-1.36, p = 0.086) and frailty. There was no pleiotropy in the results. The sensitivity analysis based on the leave-one-out method showed that the individual single nucleotide polymorphisms (SNPs) did not affect the robustness of the results. Conclusion: The current MR investigation shows a causal association between PM2.5 and frailty. Frailty's detrimental progression may be slowed down with the help of air pollution prevention and control.

Effects of novel coronavirus Omicron variant infection on pregnancy outcomes: a retrospective cohort study from Guangzhou.

Objective: Since 2022, Omicron has been circulating in China as a major variant of the novel coronavirus, but the effects of infection with Omicron variants on pregnant women and newborns are unknown. The purpose of this study was to determine the clinical characteristics of Omicron infection during pregnancy and its effect on pregnancy outcomes. Methods: This study retrospectively analyzed the data of 93 confirmed cases of novel coronavirus infection and 109 non-infected patients admitted to the isolation ward of Guangdong Maternal and Child Health Hospital from December 1, 2022 to January 31, 2023, and statistically analyzed the clinical features of Omicron variant infection during pregnancy and its impact on pregnancy outcomes. Further effects of underlying diseases on Omicron infection in pregnant women were analyzed. Results: The incubation period of COVID-19 infection was 0.99±0.86 days, 94.38% of patients had fever or other respiratory symptoms, the lymphocyte count in the infected group was lower than that in the uninfected group, and the lymphocyte count was further reduced in the patients with pregnancy complications or complications. Compared with the uninfected group, APTT and PT were prolonged, platelet count and fibrinogen were decreased in the infected group, all of which had statistical significance. COVID-19 infection during pregnancy increased the rate of cesarean section compared to uninfected pregnant patients, and COVID-19 infection in gestational diabetes resulted in a 4.19-fold increase in cesarean section rate. There was no statistically significant difference in gestational age between the two groups. The incidence of intrauterine distress, turbidity of amniotic fluid and neonatal respiratory distress were higher in the infection group. No positive cases of neonatal COVID-19 infection have been found. Conclusion: The patients infected with omicron during pregnancy often have febrile respiratory symptoms with lymphocyopenia, but the incidence of severe disease is low. Both Omicron infection and gestational diabetes further increase the incidence of cesarean section, and this study found no evidence of vertical transmission of Omicron.

Investigating the molecular mechanism of traditional Chinese medicine for the treatment of placental syndromes by influencing inflammatory cytokines using the Mendelian randomization and molecular docking technology.

Introduction: Placental syndromes, which include pregnancy loss, preterm birth, gestational diabetes mellitus (GDM), and hypertensive disorders in pregnancy (HDP), have a strong association with disorder inflammatory reactions. Nonetheless, the exact causal relationship has not been established. This study aims to investigate the causal relationship between placental syndromes and inflammatory cytokines utilizing Mendelian randomization (MR). Additionally, we examined the interaction between small molecular compounds derived from traditional Chinese medicine and inflammatory cytokines using molecular docking method. Methods: After obtaining the data of inflammatory cytokines and placental syndromes, as well as establishing single nucleotide polymorphisms (SNPs), we employed the inverse variance weighted (IVW) method to assess the causal relationship. We also accessed the heterogeneity and the horizontal pleiotropy of these data. The "ClusterProfiler" R package was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analyses. The protein-protein interaction (PPI) network was constructed using STRING database. AutoDock Vina software was used for molecular docking, and Discovery Studio 2019 was used for visualization purposes. Results: We found that the growth regulated oncogene A (GROA) and interleukin-9 (IL-9) were associated with the development of pregnancy hypertension, whereas interleukin-10 (IL-10) and hepatocyte growth factor (HGF) were linked to the occurrence of preeclampsia. Moreover, there were correlations observed between interleukin-18 (IL-18), IL-10, macrophage colony-stimulating factor (MCSF), and platelet-derived growth factor BB (PDGFbb) in cases of chronic hypertension combined with pregnancy (CHP). Additionally, macrophage migration inhibitory factor (MIF) exhibited a connection with GDM, and TNF related apoptosis inducing ligand (TRAIL) demonstrated a causal relationship with preterm birth. It is plausible to suggest that interleukin-1ß (IL-1ß) might contribute to the promotion of pregnancy loss. All of the binding free energy values of small molecular compounds with inflammatory cytokines were below -5.0 kcal/mol. Furthermore, all of the RMSD values were less than 2. Conclusions: GROA, IL-1ß, IL-9, IL-10, IL-18, MIF, MCSF, HGF, PDGFbb and TRAIL were found to be causally associated with placental syndromes. Molecular docking analysis revealed that small molecular compounds, such as puerarin, magnolol, atractylenolide I, paeoniflorin, tumulosic acid and wogonin, are closely bound to these inflammatory cytokines.

Epidemiology and clinical features of maternal sepsis: A retrospective study of whole pregnancy period.

Maternal sepsis results in poor outcomes such as fetal or maternal death. The incidence and mortality rates of maternal sepsis vary in different places because of differences in economic development, race and medical conditions. Identifying the clinical features and determining possible mechanisms for avoiding morbidity and preventing poor outcomes would benefit committed patients. Therefore, this was an epidemiological study at a maternity transfer center in Southeast China that aimed to identify local disease features of maternal sepsis. To investigate the incidence and risk factors associated with maternal sepsis and its progression to severe sepsis in a large population-based birth cohort. This local epidemiological study was conducted in at a tertiary care center in Guangzhou, China, from 2015 to 2019. A total of 74,969 pregnant women experiencing childbirth were included in this study; Of these, 74 patients with maternal sepsis were diagnosed according to the sepsis criterion, and 118 patients without sepsis in the same period were selected randomly as the control group to study possible reasons for postpartum sepsis. This retrospective analysis covered the entire period from the first trimester to puerperium. Clinical data were collected using the hospital's electronic medical record system. Multivariate logistic regression was used to analyze risk factors for maternal sepsis. The incidences of maternal sepsis, the maternal mortality, and the fetal mortality were 0.099%, 0.004%, and 0.007%, respectively. Septic shock was associated with a higher severity of illness. All poor outcomes (maternal or fetal death) occurred during pregnancy. Postpartum sepsis had the longest onset period, and was associated with premature rupture of fetal membranes and preeclampsia. Sepsis is an important cause of both maternal and fetal mortality. Herein, we describe an epidemiological study that evaluated the incidence, development, and prognosis of local maternal sepsis. Furthermore, the characteristics of maternal sepsis are likely due to unknown pathological mechanisms, and patients would benefit from identifying more effective treatments for maternal sepsis.

Prediction of Differentially Expressed Genes and a Diagnostic Signature of Preeclampsia via Integrated Bioinformatics Analysis.

Background: Preeclampsia (PE), which has a high incidence rate worldwide, is a potentially dangerous syndrome to pregnant women and newborns. However, the exact mechanism of its pathogenesis is still unclear. In this study, we used bioinformatics analysis to identify hub genes, establish a logistic model, and study immune cell infiltration to clarify the physiopathogenesis of PE. Methods: We downloaded the GSE75010 and GSE10588 datasets from the GEO database and performed weighted gene coexpression network analysis (WGCNA) as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The online search tool for the retrieval of interacting genes and Cytoscape software were used to identify hub genes, which were then used to establish a logistic model. We also analyzed immune cell infiltration. Finally, we verified the expression of the genes included in the predictive model via RT-PCR. Results: A total of 100 and 212 differently expressed genes were identified in the GSE75010 and GSE10588 datasets, respectively, and after overlapping with WGCNA results, 17 genes were identified. KEGG and GO analyses further indicated the involvement of these genes in bioprocesses, such as gonadotropin secretion, immune cell infiltration, and the SMAD and MAPK pathways. Additionally, protein-protein interaction network analysis identified 10 hub genes, six (FLT1, FLNB, FSTL3, INHA, TREM1, and SLCO4A1) of which were used to establish a logistic model for PE. RT-PCR analysis also confirmed that, except FSTL3, these genes were upregulated in PE. Our results also indicated that macrophages played the most important role in immune cell infiltration in PE. Conclusion: This study identified 10 hub genes in PE and used 6 of them to establish a logistic model and also analyzed immune cell infiltration. These findings may enhance the understanding of PE and enable the identification of potential therapeutic targets for PE.

Preparation of N,O-carboxymethyl chitosan coated alginate microcapsules and their application to Bifidobacterium longum BIOMA 5920.

In order to greatly improve vitality of probiotic bacteria within the application, a novel biocompatible vehicle, N,O-carboxymethyl chitosan (NOCs) with appropriate degrees of substitution coat alginate (ALg) microparticles, was prepared by electrostatic droplet generation. The amount of chitosan (Cs) and N,O-carboxymethyl chitosan (NOCs) coated on the ALg microparticles was determined by differential scanning calorimetry. The surface morphology of ALg microparticles, Cs coated ALg microparticles and NOCs coated ALg microparticles was determined using scanning electron microscopy. The coating thickness of Cs coated ALg microparticles and that of NOCs coated ALg microparticles was directly observed with confocal laser scanning microscopy. In order to assess pH sensitivity of microparticles, the bovine serum albumin release from the microspheres was tested in acid solution (pH 2.0) for 2 h and subsequently in alkaline solution (pH 7.0) for 2 h. The survival of Bifidobacterium longum BIOMA 5920 loaded in NOCs coated with ALg microparticle was improved in simulated gastric juice (pH 2.0, for 2 h) compared to that of B. longum BIOMA 5920 loaded in ALg microparticles and Cs coated ALg microparticles. After incubation in simulated intestinal juices (pH 7.0, 2 h), the release of microencapsulated B. longum BIOMA 5920 was investigated.

[Clinical evaluation of the antioxidant activity of astragalus in women with gestational diabetes].

OBJECTIVE: To evaluate the antioxidant activity of astragalus and its therapeutic effect on gestational diabetes. METHODS: Eighty-four pregnant women with gestational diabetes were divided into insulin and insulin plus astragalus groups after regular dietary control and insulin treatment to maintain stable blood glucose level. The 43 patients in insulin group received insulin injection, whereas the 41 patients in the other group received treatment with both insulin and astragalus. The SOD activity, MDA level, blood lipids and renal function were determined in both groups after the treatments. RESULTS: The patients with both insulin and astragalus treatments showed significantly increased serum SOD activity and decreased MDA level, renal function and blood lipids in comparison with those with exclusive insulin treatment. CONCLUSION: Astragalus can effectively control blood glucose, reduce the free radicals, and promote the antioxidative activity, and may play a role in the prevention and treatment of gestational diabetes.